Evaluation of left ventricular function is of interest for both diagnostic and therapeutic applications. During normal cardiac function, the left atrium, the left ventricle, and the right ventricle observe consistent time-dependent relationships during the systolic (contractile) phase and the diastolic (relaxation) phase of the cardiac cycle. During cardiac dysfunction associated with pathological conditions or following cardiac-related surgical procedures, these time-dependent mechanical relationships are often altered. This alteration, when combined with the effects of weakened cardiac muscles, reduces the ability of the ventricle to generate contractile strength resulting in hemodynamic insufficiency. A method for quantifying the degree of ventricular asynchrony would be useful for both diagnostic purposes and in selecting and optimizing a therapy to restore ventricular synchrony.
Ventricular dyssynchrony following coronary artery bypass graft (CABG) surgery is a problem encountered relatively often, requiring postoperative temporary pacing. Atrio-biventricular pacing has been found to improve post-operative hemodynamics following such procedures. A widely accepted, standardized method for selecting pacing sites and pacing intervals that provide the greatest hemodynamic benefit to the patient during the critical recovery phase, however, has not been available.
Chronic ventricular resynchronization therapy has been clinically demonstrated to improve indices of cardiac function in patients suffering from congestive heart failure. Cardiac pacing may be applied to one or both ventricles or multiple heart chambers, including one or both atria, to improve cardiac chamber coordination, which in turn is thought to improve cardiac output and pumping efficiency. Clinical follow-up of patients undergoing resynchronization therapy has shown improvements in hemodynamic measures of cardiac function, left ventricular volumes, and wall motion. However, not all patients respond favorably to cardiac resynchronization therapy. Physicians are challenged in selecting patients that will benefit and in selecting the optimal pacing intervals applied to resynchronize the heart chamber contractions.
Selection of pacing parameters may be based on echocardiographic studies performed to determine the settings resulting in the best hemodynamic response. Significant hemodynamic changes may not always be acutely observable in an individual patient using non-invasive monitoring methods. Selection of parameters may therefore be based on avoidance of altered or impeded ventricular filling. In the MIRACLE clinical trial conducted to evaluate resynchronization therapy, the A-V interval was optimized individually in patients by shortening the A-V interval to maximize LV filling without truncating the atrial contribution as observed by echocardiography.
Doppler tissue imaging has been used clinically to investigate coordination between septal and lateral wall motion and has been proposed as a method for predicting which patients are likely to benefit from resynchronization therapy. Evidence suggests patient response is dependent on the degree of ventricular synchrony before and after therapy.
Echocardiographic approaches, however, provide only an open-loop method for selecting pacing intervals. After evaluating the hemodynamic effect of varying combinations of pacing intervals, a physician must manually select and program the desired parameters and assume that the patient's device optimal settings remain unchanged until a subsequent re-optimization visit. Furthermore, an echocardiographic procedure for optimizing resynchronization therapy can require substantial time and personnel. An automated method for selecting pacing intervals during resynchronization therapy is therefore desirable.
Multichamber pacing systems having automated selection of pacing intervals have been proposed. A four-chamber pacing system that includes impedance sensing for determining the timing of right heart valve closure or right ventricular contraction and adjusting the timing of delivery of left ventricular pace pulses is generally disclosed in U.S. Pat. No. 6,223,082 issued to Bakels, et al., incorporated herein by reference in its entirety. Programmable coupling intervals selected so as to provide optimal hemodynamic benefit to the patient in an implantable multichamber cardiac stimulation device are generally disclosed in U.S. Pat. No. 6,473,645 issued to Levine, incorporated herein by reference in its entirety.
It would be desirable to provide a method for automatically optimizing a resynchronization therapy based on a parameter indicative of ventricular synchrony. Evaluation of hemodynamic or electrocardiographic (ECG) parameters may be used in assessing ventricular synchrony. QRS width is generally considered to widen with ventricular asynchrony. However, measurement of QRS width is typically not a sensitive measure for indicating improvements in ventricular synchrony. Direct analysis of right and left ventricular pressure waveforms is another method of assessing ventricular synchrony. Comparison of rapid pressure changes in the left and right ventricles during systole, however, becomes problematic due to limited time resolution. One approach to eliminating a time resolution limitation is to evaluate right ventricular pressure as a function of left ventricular pressure, or, conversely, left ventricular pressure as a function of right ventricular pressure. A method and apparatus for determining whether a heart failure patient will benefit from pacing therapy involving calculating the area associated with an RVP versus LVP loop is generally disclosed in U.S. Pat. No. 6,280,389 issued to Ding et al., incorporated herein by reference in its entirety.
In experimental studies performed by the inventor of the present invention, integration of the RVP-LVP loop did not differentiate between normal and heart failure subjects unless the integration method took into account the direction of the RVP-LVP loop pathway, resulting in a vector having a mathematically positive or negative value. Furthermore, unless a direction-dependent method of integration was used, the resulting RVP-LVP loop area was dependent on heart rate. A parameter for assessing ventricular synchrony should be independent of heart rate.
Other options for treating a heart failure patient include ventricular assist devices (VADs). End-stage heart failure patients may be implanted with a left ventricular assist device (LVAD) while awaiting a heart transplant.
Heart failure patients undergoing surgery may also be provided with an LVAD to acutely unload the ventricle to promote recovery. A major problem faced by physicians, however, is that 20% to 30% of patients treated with an LVAD develop right ventricular failure that is refractory to medical treatment. Right ventricular function may decline as a result of changes to right ventricular preload and after load resulting from abnormal pressure imbalances between the left and right ventricle as well as abnormal wall movement observed as septal shifting and free wall asynchronous bulging. Maintaining a greater degree of synchrony between right and left ventricular pressure development may prevent the demise of right ventricular function in the presence of an LVAD.
From the above discussion, it is apparent that, in the evaluation of heart failure patients for therapy selection, in the evaluation of therapy effectiveness, and in improving the understanding of heart failure and heart failure therapy mechanisms, a reliable metric of ventricular synchronization is needed. Such a metric would be useful in optimizing resynchronization therapy delivery or VAD operation. A reliable metric should be independent of heart rate and dependent on heart failure. Furthermore, such a metric preferably distinguishes between left-led and right-led ventricular pressure development such that resynchronization therapy or VAD operation may be adjusted appropriately for restoring ventricular synchrony and promoting myocardial recovery.